1r8u

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{{STRUCTURE_1r8u| PDB=1r8u | SCENE= }}
{{STRUCTURE_1r8u| PDB=1r8u | SCENE= }}
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'''NMR structure of CBP TAZ1/CITED2 complex'''
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===NMR structure of CBP TAZ1/CITED2 complex===
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==Overview==
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The TAZ1 domain of the homologous transcriptional coactivators CREB-binding protein (CBP) and p300 forms a complex with CITED2 (CBP/p300-interacting transactivator with ED-rich tail), inhibiting the activity of the hypoxia inducible factor (HIF-1alpha) and thereby attenuating the cellular response to low tissue oxygen concentration. We report the NMR structure of the CBP TAZ1 domain bound to the activation domain of CIT-ED2. The structure of TAZ1, consisting of four alpha-helices (alpha(1)-alpha(4)) stabilized by three zinc atoms, is very similar in the CITED2 and HIF-1alpha complexes. The activation domain of CITED2 is unstructured when free and folds upon binding, forming a helix (termed alpha(A)) and an extended structure that wraps around TAZ1. The CITED2 alpha(A) helix packs in the TAZ1 alpha(1)/alpha(4) interface, a site that forms weak interactions with the poorly defined aminoterminal alpha-helix of HIF-1alpha. CITED2 and HIF-1alpha both contain a four residue motif, LP(E/Q)L, which binds in the TAZ1 alpha(1)/alpha(2)/alpha(3) junction in each complex. The carboxyl-terminal region of CITED2 forms an extended structure with hydrophobic contacts in the TAZ1 alpha(1)/alpha(3) interface in the site occupied by the HIF-1alpha alpha(B) helix. CITED2 does not bind at all to the TAZ1 site occupied by the HIF-1alpha carboxyl-terminal helix. The HIF-1alpha and CITED2 domains utilize partly overlapping surfaces of TAZ1 to achieve high affinity binding and to compete effectively with each other for interaction with CBP/p300; CITED2 and HIF-1alpha use these binding sites differently to maintain similar binding affinities in order to displace each other in a feedback loop during the hypoxic response.
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{{ABSTRACT_PUBMED_14594809}}
==About this Structure==
==About this Structure==
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1R8U is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R8U OCA].
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1R8U is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1R8U OCA].
==Reference==
==Reference==
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[[Category: Taz zinc finger]]
[[Category: Taz zinc finger]]
[[Category: Zinc-binding motif]]
[[Category: Zinc-binding motif]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 07:13:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:20:45 2008''

Revision as of 01:20, 28 July 2008

Image:1r8u.png

Template:STRUCTURE 1r8u

NMR structure of CBP TAZ1/CITED2 complex

Template:ABSTRACT PUBMED 14594809

About this Structure

1R8U is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Full experimental information is available from OCA.

Reference

Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2: regulation by competition between intrinsically unstructured ligands for non-identical binding sites., De Guzman RN, Martinez-Yamout MA, Dyson HJ, Wright PE, J Biol Chem. 2004 Jan 23;279(4):3042-9. Epub 2003 Oct 31. PMID:14594809

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